ELM 1 Receptors 101 Flashcards
Q: What is a ligand?
A: A molecule that binds to a receptor.
Q: What is an agonist?
A: A ligand that binds to a receptor and activates it.
Q: What is an antagonist?
A: A ligand that binds to a receptor and prevents its activation, blocking the agonist binding site (competitive) or acting at a different site.
Q: What is a subunit in the context of receptors?
A: A component protein of a receptor, with receptors made up of multiple subunits held together by non-covalent bonds.
Q: Define monomer, dimer, trimer, tetramer, pentamer, and hexamer.
A: A monomer has 1 subunit, a dimer has 2 subunits, a trimer has 3 subunits, a tetramer has 4 subunits, a pentamer has 5 subunits, and a hexamer has 6 subunits.
Q: What is a kinase?
A: An enzyme that phosphorylates its targets, regulating their activity by adding phosphate groups to amino acids with an OH group (tyrosine, serine, threonine).
Q: What is an allosteric modulator?
A: A drug that binds to a site distinct from the agonist site and changes receptor behavior, which can be positive or negative.
Q: What is the Greek letter for alpha, beta, gamma, delta, and epsilon?
A: α - alpha, β - beta, γ - gamma, δ - delta, ε - epsilon.
Q: How do proteins and drugs interact in terms of size and binding?
A: Proteins are much larger (400,000 Da) compared to drugs (500 Da), so drugs contact only a small specific part of their target, the binding domain.
Q: What types of bonds do most drugs form with their protein targets?
A: Most drugs form reversible bonds, which include hydrogen bonds, van der Waals forces, hydrophobic bonds, dipole-dipole interactions, dipole-ion interactions, and ionic bonds.
Q: What is the significance of reversible vs. irreversible drug binding?
A: Reversible binding means the drug’s effect is temporary and allows for repeated dosing. Irreversible binding requires the body to synthesize new copies of the target protein for the effect to wear off.
Q: Name three drugs that form covalent bonds with their targets.
A: Aspirin, clopidogrel, and omeprazole.
Q: What is a receptor in pharmacology?
A: A protein that binds a molecular message and passes the information contained in that message on in a different form (signal transduction).
Q: What percentage of drug targets are receptors, and which type is most common?
A: 40-60% of drug targets are receptors, with more than half being G protein-coupled receptors.
Q: What is a superfamily in the context of proteins?
A: A broad grouping of proteins related to each other in structure and function.
Q: What is the organizational hierarchy within a protein superfamily?
A: Superfamily, family, subfamily.
Q: What is an example of a protein superfamily?
A: G protein-coupled receptors (GPCRs).
Q: How many members are there in the GPCR superfamily, and how are they categorized?
A: Over 800 members, divided into 6 families based on amino acid sequence and functional similarities.
Q: What is the largest family within the GPCR superfamily?
A: The Rhodopsin-like family (Family A) with over 600 members.
Q: How many subfamilies are in the Rhodopsin-like family?
A: 19 subfamilies.
Q: What is an example of receptors in Family A with multiple subtypes?
A: Muscarinic acetylcholine receptors, with 5 different types each coded by a separate gene.
Q: How do protein superfamilies arise?
A: From a single ancestral protein through gene duplication and subsequent mutation.
Q: What happens during gene duplication?
A: An organism gets a redundant copy of an essential gene, allowing one copy to acquire mutations and potentially gain a new function.
Q: What are the evolutionary advantages of protein diversity?
A: Greater flexibility and adaptability to the environment, and the potential for new functions and interactions.
Q: How can the diversity of receptors aid drug development?
A: By targeting specific receptor subtypes to treat different conditions more effectively.
Q: How many types of adrenoceptors are there, and how are they classified?
A: Nine types, classified into alpha (α) and beta (β) subtypes.
Q: What is the role of the β1 adrenoceptor, and how can it be targeted in drug development?
A: Heavily expressed in the heart, increases heart rate and force of contraction. Blocking β1 without affecting β2 is useful for treating angina (e.g., atenolol).
Q: What is the role of the β2 adrenoceptor, and how can it be targeted in drug development?
A: Expressed in bronchial smooth muscle, causes airway dilation. Activating β2 without affecting β1 is useful for treating asthma (e.g., salbutamol).
Q: Why is receptor diversity vital for drug development?
A: It allows for the creation of drugs that can specifically target different receptor subtypes for precise therapeutic effects.
Q: What are ligand-gated ion channels (LGICs)?
A: Transmembrane proteins with built-in ion channels that open in response to the binding of a neurotransmitter ligand, allowing ions to cross the membrane and change cell behavior.
Q: How many agonist binding sites do most ligand-gated ion channels have, and what is required for channel opening?
A: Most have 2 binding sites for agonists, and both must be occupied for the ion channel to open.
Q: What is selective permeability in the context of LGICs?
A: The property that allows only specific types of ions to pass through the ion channel based on the concentration gradient.
Q: What happens to an LGIC when the agonist dissociates?
A: The receptor returns to its inactive state, and the ion channel closes.
Q: What is the general structure of pentameric LGICs?
A: They consist of 5 subunits arranged in a ring around an integral ion channel, with each subunit having 4 transmembrane domains and a large N-terminal extracellular domain for agonist binding.
Q: How many transmembrane domains do the subunits of pentameric LGICs have?
A: Four transmembrane domains.
Q: What forms part of the ion channel lining in pentameric LGICs?
A: The second transmembrane domain of each subunit.
Q: In which kingdoms of life are pentameric LGICs found?
A: They are present in all three kingdoms of life (Archaea, Bacteria, and Eukarya).
Q: Describe the role of the N-terminal extracellular domain in pentameric LGICs.
A: It contributes to the agonist binding sites.
Q: What determines the direction of ion movement through an LGIC?
A: The concentration gradient of the ions.
Q: What type of channels are nAChRs?
A: Cation channels permeable to Na+, K+, and Ca2+.
Q: What occurs when nAChRs are activated?
A: Na+ and Ca2+ enter the cell, depolarizing the membrane and producing excitatory effects.
Q: What is the natural agonist of nAChRs, and what else can activate them?
A: The natural agonist is acetylcholine (ACh), and they can also be activated by nicotine.
Q: What is the physiological importance of nAChRs?
A: They are responsible for fast excitatory transmission between motor neurons and skeletal muscle and also play a role in autonomic ganglia and neurotransmitter modulation in the CNS.
Q: Why are nAChRs important pharmacologically in skeletal muscles?
A: They are targets of drugs used to block neuromuscular transmission to relax muscles during surgery.
Q: Why are brain nAChRs significant in pharmacology?
A: They are the targets of nicotine and drugs that treat addiction.
Q: How were nAChRs first identified?
A: They were identified in skeletal muscle due to the availability of large amounts and the presence of several snake toxins that target these receptors.
Q: How many subunits are in the nAChR family, and how do they form receptors?
A: There are 16 subunits that come together in different combinations to form various receptor subtypes.
Q: What are the five different classes of nAChR subunits?
A: α (alpha), β (beta), γ (gamma), δ (delta), and ε (epsilon).
Q: How many different alpha and beta subunits exist in humans?
A: Nine alpha subunits (α1-7, α9, α10) and four beta subunits (β1-4).
Q: What are the three most important classes of nAChRs based on location?
A: Skeletal muscle, autonomic ganglia, and CNS (main target of nicotine).
Q: What role does nAChRs’ ability to regulate dopamine play in nicotine addiction?
A: It makes nicotine highly addictive by modulating the release of dopamine in the CNS.
Q: What type of channels are GABA A receptors?
A: Chloride channels that, when activated, allow chloride ions to enter the cell.
Q: What effect does the activation of GABA A receptors have on a cell?
A: Hyperpolarizes the cell, making it less excitable.
